Process for producing cis-3-(2,2-disubstituted-ethenyl)-2,2-dimethylcyclopropanecarboxylic acid and intermediates

ABSTRACT

Novel intermediates for production of insecticidal cis-3-(2,2-disubstituted-ethenyl)-2,2-dimethylcyclopropanecarboxylates, processes for preparing the intermediates, and processes for preparing the final product insecticides via a novel bicyclic lactone intermediate are described and exemplified.

This application is a division, of application Ser. No. 090,218, filedNov. 1, 1979, issued Dec. 2, 1980 as U.S. Pat. No. 4,237,058.

This invention relates to novel intermediates for production ofinsecticidalcis-3-(2,2-disubstituted-ethenyl)-2,2-dimethylcyclopropanecarboxylatesand to processes for preparing the intermediates.

U.S. Pat. No. 4,024,163 discloses3-(2,2-dihaloethenyl)-2,2-dimethylcyclopropanecarboxylic acids, loweralkyl esters thereof, and insecticidal pyrethroid esters made from them.The intermediate acids may be converted to insecticidaly activepyrethroids by treatment with thionyl chloride to produce acorresponding acid chloride, followed by reaction with an appropriatealcohol, such as 3-phenoxybenzyl alcohol, to produce the correspondinginsecticidal ester.

These esters and acids are known to exist as cis and trans geometricalisomers; and it is also known that the cis isomers of a givendihaloethenylcyclopropanecarboxylate are generally more activeinsecticidally than the corresponding trans isomers. As a result,substantial research effort has been directed to processes for producingcis geometrical isomers of these acids and esters, substantially free oftrans acids or esters.

Belgian Pat. No. 868,445, published Dec. 12, 1978 discloses the use of abicyclic lactone of the formula ##STR1## as an intermediate in thepreparation ofcis-3(2,2-dihaloethenyl)-2,2-dimethylcyclopropanecarboxylic acid, anintermediate for the corresponding cis-pyrethroid. The bicyclic lactoneis prepared by reacting caronaldehydic acid with a haloform, thendehydrating the resulting acid. The caronaldehydic acid used as astarting material, and processes for its preparation are disclosed inU.S. Pat. Nos. 3,723,469 and 4,132,177.

In one aspect of the present invention there is provided a novelcompound of formula I ##STR2## and a process for its preparation. Inanother aspect of the present invention there is provided a novelbicyclic lactone of formula II ##STR3## and a method for itspreparation. In another aspect of the present invention there isprovided a method for producing a cis-cyclopropanecarboxylic acid suchas cis-3-(2,2-dihaloethenyl)-2,2-dimethylcyclopropanecarboxylic acid orcis-3-(2-halo-2-trihalomethylethenyl)-2,2-dimethylcyclopropanecarboxylicacid by simultaneous ring opening and decarboxylation of the bicycliclactone (II).

Throughout the specification and claims, unless a contrary meaning isspecified, the terms halo or halogen mean bromine, chlorine or fluorinewhich may be independently selected. Similarly the term "lower" asapplied to a hydrocarbyl group means having 1 to 4 carbon atoms,straight or branched chain.

The first aspect of this invention comprises a compound of the formula##STR4## wherein Y is a chlorine or bromine atom; X₁ and X₂ are the sameor different and each is a halogen atom, a trichloromethyl group, or atrifluoromethyl, and R is an alkyl group of 1 to 4 carbon atoms,preferably methyl or ethyl, with the proviso that Y is a bromine atomwhen at least one of X¹ and X² is a bromine atom. Preferred compoundsare those in which X¹ is chlorine or bromine and X² is the same as X¹ oris trifluoromethyl. The compounds of formula I are prepared by reacting3,4-dihydro-4,4-dimethyl-2H-pyran-2-one with a lower alkyl haloacetateas follows; R, X¹, X², and Y being as specified above: ##STR5##

The addition of the haloacetate radical to the C-6 position, rather thanthe C-5 position of the dihydropyranone is quite surprising. It is knownthat free radicals having an unpaired electron α to an -OR group (C-6 ofthe dihydropyranone may be considered α to an OR group) have increasedstability at that α-position. See J. March, Advanced Organic Chemistry,2nd ed., p. 632, McGraw-Hill, NY (1967, 1968). One would thus expectradical addition to occur at the unstabilized C-5 position. Once theactual course of reaction is known, steric hindrance due to thegem-dimethyl group could be postulated as hindering addition at C-5,leading to addition at C-6, but no reference has been found which wouldenable one skilled in the art to predict with the required degree ofcertainty whether, or to what extent, the gem-dimethyl group would beexpected to influence the addition. Thus, the results achieved areunexpected since one would not have predicted in advance the course thereaction took.

The foregoing reaction is conducted in the presence of a suitableaddition catalyst. Suitable catalysts include free radical initiators,light, a transition metal salt, or a complex between a transition metalsalt and electron donors such as organic amines, carbon monoxide,acetylacetone, and the like.

Suitable free radical initiators include azobisisobutyronitrile (AIBN),benzoyl peroxide (BPO), acetyl peroxide, di-t-butyl peroxide, t-butylperacetate, t-butyl perbenzoate, t-butyl perphthalate, t-butylhydroperoxide and the like.

Suitable transition metal salts which may be employed include cuprouschloride, cupric chloride, ferrous chloride, ferric chloride, cobalt,nickel, zinc, palladium, rhodium or ruthenium chloride, copper cyanide,copper thiocyanide, copper oxide, copper sulfide, copper or ironacetate, iron citrate, iron sulfate, iron oxide, copper or ironacetylacetonate and the like. Cuprous chloride is preferred.

Examples of organic amines which can be used in conjunction with thesetransition metal salts include aliphatic amines such as n-butylamine,diisopropylamine, triethylamine, cyclohexylamine, ethylenediamine andthe like; aromatic amines such as aniline or toluidine; or amine saltssuch as diethylamine hydrochloride.

The reaction is preferably conducted at elevated temperature, suitablyabove about 100° C., advantageously in the range of 100°-300° C., morepreferably about 150° C. to about 175° C.

The haloacetate and dihydropyranone are suitably used in about equimolaramounts, but an excess of either may be used if desired.

The haloacetate is prepared by esterification of commercially availabletrihaloacetates or by procedures or from compounds described in J. Am.Chem. Soc., 78, 5639 (1956); Bull. Acad. Sci. USSR 1966, 2049 (1966); orC. A. 73, 87470 g (1970) and German Offenlegungschrift 1,900,758referred to therein.

Another aspect of this invention comprises a novel bicyclic lactone ofthe formula ##STR6## in which X¹ and X² are the same or different andeach is a halogen atom, a trichloromethyl group, or a trifluoromethylgroup; and R is an alkyl group of 1 to 4 carbon atoms, preferably methylor ethyl. In the preferred embodiment X¹ is bromine or chlorine and X²is the same as X¹ or is trifluoromethyl.

This compound is prepared by reacting the compound of formula I with abase to remove one molar equivalent of hydrogen halide per mole of I.

The base employed in this reaction is suitably an alkali metal alkoxideor hydride. For example, one may employ such alkoxides as sodiummethoxide, sodium ethoxide, sodium t-butoxide, potassium t-butoxide,sodium t-pentoxide, or potassium t-pentoxide. The preferred bases arethe tertiary alkoxides of 4 or 5 carbon atoms such as sodium t-butoxide.About one molar equivalent per mole of substrate (I) or a slight molarexcess of base may be employed. Other strong bases such as sodiumhydride may also be suitable.

The reaction is suitably conducted in the presence of a solvent. A widerange of solvents may be employed, including alkanols having 1 to 6carbon atoms, such as methanol, ethanol, t-butanol, or t-pentanol;ethers having 4 to 6 carbon atoms, such as diethyl ether,tetrahydrofuran, dimethoxyethane or dioxane; or aromatic hydrocarbons of6 to 10 carbon atoms, such as benzene or toluene.

This dehydrohalogenation reaction is suitably conducted at about roomtemperature or below, for example at a temperature in the range of -25°C. to about 30° C.

In accordance with another aspect of the invention a cis isomer of acompound of formula III ##STR7## wherein X¹ and X² are the same ordifferent and each is a halogen atom, a trichloromethyl group or atrifluoromethyl group, preferably X¹ is bromine or chlorine and X² isthe same as X¹ or is a trifluoromethyl group, is prepared by heating thecorresponding bicyclic lactone (II) in the presence of a decarboxylationcatalyst and a polar aprotic solvent.

Suitable catalysts include alkali metal salts, such as lithium iodide,bromide, chloride, selenide, thiocyanate, cyanide; sodium iodide,cyanide; potassium iodide, cyanide, and the like; amines such astriethylamine, 1,5-diazabicyclo[3.4.0]non-5-ene and the like; andsilanes such as trimethylsilyl iodide and the like. Alkali metal iodidesor cyanides are preferred.

Suitable solvents include polar aprotic solvents such as dimethylsulfoxide, dimethylformamide, dimethylacetamide,hexamethylphosphortriamide, sulfolane, 1-methyl-2-pyrrolidone, and thelike, and solvents such as pyridine, 2,6-lutidine, 2,4,6-collidone, andthe like.

The reaction is suitably conducted at a temperature in the range of 60°C. to about 200° C.

The following examples illustrate preparation of4,4-dimethyl-2H-pyran-2-one, the starting material for the presentinvention.

EXAMPLE 1 Preparation of ethyl 3,3-dimethyl-5-phenylthiopentanoate

A mixture of 60.0 g (0.384 mole) of ethyl 3,3-dimethyl-4-pentenoate and90.0 g (0.817 mole) of benzenethiol was irradiated with a 100 wattincandescent light bulb at 120°-130° C. for 4 days. Benzoyl peroxide(1.8 g, 0.0074 mole) was added to the reaction vessel in 300 mgincrements at various times throughout the 4-day irradiation period fora total of six such additions. Distillation of the reaction mixture gave102.3 g (96% yield) of ethyl 3,3-dimethyl-5-phenylthiopentanoate, 96.3%purity (glpc), bp 130° C./27 Pa (0.2 mm Hg).

EXAMPLE 2 Preparation of ethyl5-chloro-3,3-dimethyl-5-phenylthiopentanoate

To a solution of 1.06 g (3.09 mmol) of ethyl3,3-dimethyl-5-phenylthiopentanoate in 10 ml of carbon tetrachloride wasadded 590 mg (4.4 mmol) of 1-chloro-2,5-pyrrolidinedione, and themixture was stirred at room temperature for 2 hours. The mixture wasfiltered, and the filtrate concentrated to give ethyl5-chloro-3,3-dimethyl-5-phenylthiopentanoate as an oil.

NMR Data (CDCl₃):

δ(ppm): 1.10 (6H, s), 1.20 (3H, t), 2.10 (2H, d), 2.25 (2H, s), 4.02(2H, q), 5.23 (1H, t), 7.00-7.53 (5H, m).

EXAMPLE 3 Preparation of ethyl 3,3-dimethyl-5-oxopentanoate from ethyl5-chloro-3,3-dimethyl-5-phenylthiopentanoate

The crude ethyl 5-chloro-3,3-dimethyl-5-phenylthiopentanoate fromExample 2 was dissolved in 15 ml of acetone, and the solution was addedto a mixture of 1.2 g (8.9 mmol) of cupric chloride and 1.2 g (15 mmol)of cupric oxide in 15 ml of acetone and 0.6 ml of water. The mixture wasstirred at room temperature for 30 minutes, filtered, and the filtrateconcentrated to give a residue. The residue was dissolved in methylenechloride, and the solution washed successively with an aqueous sodiumbicarbonate solution and an aqueous solution of sodium chloride. Theorganic layer was separated, dried over anhydrous magnesium sulfate,filtered, and the filtrate concentrated to give 1.0 g of ethyl3,3-dimethyl-5-oxopentanoate.

NMR Data (CCl₄):

δ(ppm): 1.11 (6H, s), 1.23 (3H, t), 2.32 (2H, s), 2.45 (2H, b.s.), 4.05(2H, q), 9.72 (1H, b.s.).

EXAMPLE 4 Preparation of 3,4-dihydro-4,4-dimethyl-2H-pyran-2-one

A solution of 11.16 g (0.065 mole) of ethyl 3,3-dimethyl-5-oxopentanoateand 11.2 g (0.073 mole) of phosphoryl chloride in 90 ml of toluene washeated under reflux for 14 hours. The mixture was diluted with ether,washed with an aqueous solution of sodium bicarbonate, dried overanhydrous magnesium sulfate, filtered, and the filtrate concentrated togive, after distillation, 3.29 g (40% yield) of3,4-dihydro-4,4-dimethyl-2H-pyran-2-one, bp 105°-110° C./2670 Pa (20 mmHg).

NMR Data (CDCl₃):

δ(ppm): 1.10 (6H, s), 2.47 (2H, s), 5.12 (1H, d, J=6 Hz), 6.33 (1H, d,J=6 Hz).

The following examples illustrate conversion of3,4-dihydro-4,4-dimethyl-2H-pyran-2-one to the intermediates of thisinvention by the claimed process.

EXAMPLE 5 Preparation of ethylα,α,-3-trichloro-3,4,5,6-tetrahydro-4,4-dimethyl-6-oxo-2H-pyran-2-acetate

A mixture of 3,4-dihydro-4,4-dimethyl-2H-pyran-2-one (2.6 g, 20.6 mmol),ethyl trichloroacetate (4.0 g, 20.9 mmol), and cuprous chloride (500 mg)was sealed in a test tube and heated at 150° for three days. At the endof this period the mixture was purified by column chromatography onsilica gel to give 2.1 g of ethylα,α-3-trichloro-3,4,5,6-tetrahydro-4,4-dimethyl-6-oxo-2H-pyran-2-acetate(32% yield).

NMR data (CDCl₃):

δ(ppm): 1.17 (6H, s), 1.35 (3H, t, J=7 Hz), 2.50 (1H, bd, J=17 Hz), 2.54(1H, d, J=17 Hz), 4.16 (1H, d, J=7 Hz), 4.32 (2H, q, J=7 Hz), 5.23 (1H,d, J=7 Hz).

EXAMPLE 6 Preparation of ethylα,α-dichloro-6,6-dimethyl-4-oxo-3-oxabicyclo[3.1.0]hexane-2-acetate

A solution of ethylα,α,3-trichloro-3,4,5,6-tetrahydro-4,4-dimethyl-6-oxo-2H-pyran-2-acetate(3.43 g, 10.8 mmol) in 20 ml of tetrahydrofuran was cooled to -20° C.Potassium tert-butoxide was added in small portions while the mixturewas stirred and maintained at -20° C. over a period of two hours. Atotal of 1.4 g (12.5 mmol) was added. Aqueous ammonium chloride wasadded and the mixture was extracted with methylene chloride.Purification by column chromatography gave 1.82 g of ethylα,α-dichloro-6,6-dimethyl-4-oxo-3-oxabicyclo[3.1.0]hexane-2-acetate (60%yield).

NMR data (CDCl₃):

δ(ppm): 1.22 (6H, s), 1.34 (3H, t, J=7 Hz), 2.06 (1H, dd, J=1 Hz, 6 Hz),2.24 (1H, d, J=6 Hz), 4.31 (2H, q, J=7 Hz), 4.80 (1H, bs).

EXAMPLE 7 Preparation ofcis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid

A mixture of ethylα,α-dichloro-6,6-dimethyl-4-oxo-3-oxabicyclo[3.1.0]hexane-2-acetate (500mg, 1.78 mmol) and sodium iodide (500 mg, 3.3 mmol) in 4 ml of dimethylsulfoxide was heated to 130° C. for 1.25 hours, cooled, and diluted withwater. Sodium hydroxide (200 mg) was added and the mixture was washedwith methylene chloride, acidified, and extracted with methylenechloride. The methylene chloride extract was concentrated to give 350 mgof an oil. Analysis by glpc with an internal standard showed that theoil contained 232 mg ofcis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (62%yield).

We claim:
 1. A process for preparing a compound of the formula ##STR8##wherein Y is a bromine or chlorine atom, X¹ and X² are the same ordifferent and each is a halogen atom, a trichloromethyl group, or atrifluoromethyl group, and R is an alkyl group of 1 to 4 carbon atoms,with the proviso that Y is a bromine atom when at least one of X¹ and X²is a bromine atom, which comprises reacting3,4-dihydro-4,4-dimethyl-2H-pyran-2-one with an alkyl haloacetate of theformula ##STR9## in the presence of an addition catalyst selected fromfree radical initiators, light, a transition metal salt, and atransition metal salt/amine complex.
 2. The process of claim 1 wheresaid catalyst is cuprous halide.
 3. The process of claim 1 wherein saidcatalyst is cuprous chloride.
 4. The process of claim 1, 2 or 3 whereinsaid reaction is conducted at elevated temperature.
 5. The process ofclaim 4 wherein said reaction is conducted at a temperature in the rangeof 100° C. to 300° C.
 6. A process for preparing a bicyclic lactone ofthe formula ##STR10## which comprises (1) reacting3,4-dihydro-4,4-dimethyl-2H-pyran-2-one with a lower alkyl haloacetateof the formula ##STR11## in the presence of an addition catalystselected from free radical initiators, light, a transition metal salt,and a transition metal salt/amine complex, to form a compound of theformula ##STR12## (2) reacting the resulting compound with a base toproduce said bicyclic lactone, wherein R is an alkyl group of 1 to 4carbon atoms; Y is a bromine or chlorine atom; and X¹ and X² are thesame or different and each is a halogen atom, a trichloromethyl group,or a trifluoromethyl group, with the proviso that Y is a bromine atomwhen at least one of X¹ and X² is a bromine atom.
 7. A process forpreparing acis-3-(2,2-disubstituted-ethenyl)-2,2-dimethylcyclopropanecarboxylicacid of the formula ##STR13## wherein X¹ and X² are the same ordifferent and each is a halogen atom, a trichloromethyl group, or atrifluoromethyl group, which comprises reacting a compound of theformula ##STR14## wherein R is an alkyl group of 1 to 4 carbon atoms atelevated temperature with an alkali metal halide or cyanide in thepresence of a polar aprotic solvent.
 8. A process for preparing acis-3-(2,2-disubstituted-ethenyl)-2,2-dimethylcyclopropanecarboxylateacid of the formula ##STR15## wherein X¹ and X² are the same ordifferent and each is a halogen atom, a trichloromethyl group, or atrifluoromethyl group, which comprises(1) Reacting a3,4-dihydro-4,4-dimethyl-2H-pyran-2-one with an alkyl haloacetate of theformula ##STR16## wherein R is an alkyl group of 1 to 4 carbon atoms,and Y is a bromine or chlorine atom with the proviso that Y is a bromineatom when at least one of X¹ and X² is a bromine atom, said reactionbeing conducted in the presence of an addition catalyst selected fromfree radical initiators, light, a transition metal salt, and atransition metal salt/amine complex, to form a compound of the formula##STR17## then (2) Reacting the resulting compound with a base toproduce a bicyclic lactone of the formula ##STR18## then (3) Reactingsaid bicyclic lactone with an alkali metal halide or cyanide at elevatedtemperature in the presence of a polar aprotic solvent.